In vitro detection of beta amyloid exploiting surface enhanced Raman scattering (SERS) using a nanofluidic biosensor

Alzheimer's disease (AD), a neurodegenerative disease and the most common cause of dementia, affects 4.5 million people according to the 2000 US census and is expected to triple to 13.2 million by the year 2050. Since no definitive pre-mortem tests exist to distinguish AD from mild cognitive impairment due to the natural aging process, we focus on detecting the beta amyloid (Aβ) protein, the primary component of the senile plaques characteristic of AD. We specifically detect cytotoxic species of Aβ by exploiting surface enhanced Raman scattering (SERS). Using a nanofluidic device with a bottleneck shape (a microchannel leading into a nanochannel); we trapped gold colloid particles (60 nm) at the entrance to the nanochannel, with Aβ restricted within the interstices between the aggregated nanoparticles. The continuous flow generated from pumping the solution into the device produced size-dependent trapping of the gold colloid particles, resulting in a high density of aggregated nanoparticles at this precise region, creating localized "hot spots" in the interstitial region between nanoparticles, and shifting the plasmon resonance to the near infrared region, in resonance with incident laser wavelength. With this robust sensing platform, we were able to obtain concentration-dependent SERS spectra of Aβ and of different proteins that would be present in the cerebrospinal fluid of healthy people and people with Alzheimer's disease.